Chronic apnea during REM sleep increases arterial pressure and sympathetic modulation in rats

Abstract

Study objectives Obstructive sleep apnea can induce hypertension. Apneas in REM may be particularly problematic: they are independently associated with hypertension. We examined the role of sleep stage and awakening on acute cardiovascular responses to apnea. Also, we measured cardiovascular and sympathetic changes induced by chronic sleep apnea in REM sleep. Methods We used rats with tracheal balloons and electroencephalogram and electromyogram electrodes to induce obstructive apnea during wakefulness and sleep. We measured the electrocardiogram and arterial pressure by telemetry and breathing effort with a thoracic balloon. Results Apneas induced during wakefulness caused a pressor response, intense bradycardia, and breathing effort. On termination of apnea, arterial pressure, heart rate, and breathing effort returned to basal levels within 10 s. Responses to apnea were strongly blunted when apneas were made in sleep. Post-apnea changes were also blunted when rats did not awake from apnea. Chronic sleep apnea (15 days of apnea during REM sleep, 8 h/day, 13.8 ± 2 apneas/h, average duration 12 ± 0.7 s) reduced sleep time, increased awake arterial pressure from 111 ± 6 to 118 ± 5 mmHg (p < 0.05) and increased a marker for sympathetic activity. Chronic apnea failed to change spontaneous baroreceptor sensitivity. Conclusion Our results suggest that sleep blunts the diving-like response induced by apnea and that acute post-apnea changes depend on awakening. In addition, our data confirm that two weeks of apnea during REM causes sleep disruption and increases blood pressure and sympathetic activity.

Sleep fragmentation during rapid eye movement sleep and hypertension in obstructive sleep apnea

“…The authors found that 15 days of experimentally-induced obstructive apneas in REM sleep in rats caused not only REM sleep fragmentation and decreased REM sleep time, but also increased both wake BP and sleep sympathetic modulation as measured from heart rate variability. In addition, the changes in sympathetic modulation and arterial pressure were mostly due to arousals during REM sleep [14]. These data suggest that OSA may alter the physiological response to arousals by exacerbating BP increases, possibly as a result of impaired baroreflex and/or elevated sympathetic activity.…”

“…Both abnormal respiratory events and arousals can occur during REM and NREM sleep. Recently, OSA events that occur during REM sleep have been associated with more adverse cardiovascular outcomes than those occurring during NREM, including greater risk of hypertension [14,15]. However, the relationship between arousals during REM and hypertension has not been explored.…”

Effects of Continuous Positive Airway Pressure Therapy on Nocturnal Blood Pressure Fluctuation Patterns in Patients with Obstructive Sleep Apnea

“…NBPF patterns are also likely to affect the prognosis of CVD in such patients [ 4 , 5 , 6 , 10 ]. During the sleep stage, apnea during rapid eye movement (REM) sleep was reported to lead to an increase in blood pressure (BP) and sympathetic activity in rats in approximately 2 weeks [ 14 ]. Even in healthy humans, sympathetic activity significantly increased during REM sleep [ 15 ].…”

Nocturnal Blood Pressure Fluctuations in Patients with Rapid Eye Movement-Related Obstructive Sleep Apnea

“…Obstructive apnea and hypopnea during REM sleep cause more severe hypoxemia, longer apnea duration, and higher activated sympathetic nerve activity than respiratory events during non-rapid eye movement (NREM) sleep [7,8]. It has also been reported that, after only two weeks, apnea during REM sleep resulted in an increase in blood pressure (BP) and sympathetic nerve activity in rats [9]. Even in healthy individuals, sympathetic nerve activity significantly increases during REM sleep [6].…”